Sugi Variant

Sugi Variant/LETM1

LETM1 — 335 ClinVar variants

All ClinVar germline LETM1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 144 flagged for review →

7 Pathogenic · 3 Likely pathogenic · 3 Conflicting · 23 Benign · 4 Benign/Likely benign · 133 Likely benign · 162 Uncertain significance

Full LETM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 144

Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.

Predictors vs ClinVar 1

ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.

Predictors agree, ClinVar conflicts 2

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

Predictors lean, ClinVar uncertain 109

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

Predictors split 32

The independent predictors disagree with each other — read with care.

All LETM1 variants

Pathogenic 7

  • c.2071-9C>G No assertion criteria neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction
  • p.Arg294Gln No assertion criteria LETM1-associated clinical spectrum with predominant nervous system involvement ⚠
  • p.Arg380Pro No assertion criteria LETM1-associated clinical spectrum with predominant nervous system involvement
  • p.Asp358Asn No assertion criteria LETM1-associated clinical spectrum with predominant nervous system involvement
  • p.Asp699fs No assertion criteria neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction
  • p.Ile293Asn No assertion criteria neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction
  • p.Lys252del No assertion criteria LETM1-associated clinical spectrum with predominant nervous system involvement

Likely pathogenic 3

  • p.Gln486fs Single submitter neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction
  • p.Pro300Ser Single submitter ⚠
  • p.Tyr598fs Single submitter neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction

Conflicting classifications of pathogenicity 3

  • p.Arg299fs Single submitter neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction
  • p.Gly71Ser Single submitter ⚠
  • p.Pro18Arg Single submitter Inborn genetic diseases ⚠

Benign 23

Benign/Likely benign 4

Likely benign 133

Uncertain significance 162